Association of dysmorphic intratumoral vessel with elevated lung shunt fraction in patients with hepatocellular carcinoma

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In this study, dysmorphic intratumoral vessels are commonly present in large circumscribed tumors. According to the authors’ experiments, while tumors without dysmorphic intratumor vessels generally have low LSF (Fig. 2), tumors with dysmorphic intratumor vessels appear to frequently have high LSF (Fig. 1).

Figure 2

77-year-old man with hepatocellular carcinoma (size equal to 15 cm). (a,b) No dysmorphic intratumoral vessels were found on preoperative liver computed tomography (CT) scans (a), and hepatic arteriography planning (b). In addition, there was no hepatic vein invasion or early hepatic vein enhancement on CT scan. The lung shunt fraction was 0.79%.

The present study demonstrated that the presence of a dysmorphic intratumoral vessel was an independent predictor of elevated LSF. In the literature, the presence and aneurysmal dilation of dysmorphic intratumoral vessels have been reported to be more frequently observed in poorly differentiated HCC than in well-differentiated HCC.15. Dysmorphic intratumor vessels are different from branch of hepatic artery inside tumor showing infiltrative growth16. Dysmorphic intratumoral vessels were also different from the “vascular lake” that appeared after embolization16.17. In the clinicopathological analysis conducted by Yamanaka et al., the “condensed pooling” on angiography that corresponds to the dysmorphic intratumoral vessel in the present study was confirmed by histopathological analyzes to be blood-filled cavities partially lined by the endothelium, which was a mixture of dilated tumor vessels and necrotic foci19. Possible explanations for the development of the dysmorphic intratumoral vessel included angiogenesis, distortion of the vascular architecture, and development of the arteriovenous anastomosis.15,16,20,21. Thus, dysmorphic intratumoral vessels may have dilated ducts to the hepatic vein, thereby resulting in elevated LSF values.

Several studies have been published that have identified imaging predictors for cases of high LSF9,12,13. Gaba et al. reported that invasive tumours, tumor burden >50%, portal vein invasion and arterioportal shunt were independent predictors of elevated LSF for HCC12. Olorunsola et al. reported early hepatic vein opacification and hepatic vein thrombus or tumor occlusion as independent predictors of elevated LSF13. The importance of hepatic vein invasion and early hepatic vein enhancement in predicting elevated LSF was also confirmed in the present study. The prevalence of early hepatic vein enhancement on cross-sectional arterial phase imaging in the present study (13.4%, 54/403) was similar to those reported by Olorunsola et al. (12.8%, 15/117)13 and Bermo et al. (17.3%, 59/342)9. In the present study, however, infiltrating tumor, tumor burden >50%, portal vein invasion, and arterioportal shunt were not significant for the prediction of elevated LSF. Interestingly, in this study, an elevated LSF > 20% is more frequent in the circumscribed tumor than in the infiltrating tumor. In addition, dysmorphic intratumoral vessels are rare in invasive tumors.

The results of the present study may have important implications because various imaging features were comprehensively assessed in a relatively large number of patients with HCC (n=403). Although they also extensively analyzed various imaging features, the number of HCC patients included was relatively small in the studies by Gaba et al. (n=70)12 and Olorunsola et al. (n=50)13. The study by Bermo et al. included a relatively large number of patients with HCC (n=282), but only assessed shunt-related imaging findings9.

One of the disadvantages of TARE compared to cTACE is the need to schedule angiography and lung shunt measurement, resulting in a 1-2 week delay in treatment. The results of the present study may provide important clinical implications for modifying workflow in clinical practice. Soft embolization or cTACE can reduce LSF when done before the TARE procedure22,23,24. Thus, cTACE may be recommended as an alternative initial treatment option for HCC in patients with elevated LSF > 20%. If we can identify patients with elevated LSF using preoperative imaging results with sufficiently high specificity, these patients can skip planning angiography and undergo cTACE without treatment delay. In the present study, if the patient had at least three of the four predictors of LSF > 20% on imaging, the diagnostic specificity of LSF > 20% was as high as 96.3% (Table 3). Therefore, we suggest that patients with at least three predictors of LSF >20% may benefit from planning angiography/99mTc-MAA scans are omitted, and when undergoing cTACE as initial therapy without treatment delay. In the study population of the present study, if patients with three or four imaging predictors had been considered to have an elevated LSF >20%, 20 patients could have skipped planning angiography/99mTc-MAA scans.

There are limitations to note. First, although we have suggested certain tumor diameter values ​​or dysmorphic intratumoral vessels as risk factors for elevated LSF, reproducibility issues in the measurement may exist. Second, the incidence of dysmorphic intratumoral vessels may be underestimated in this study. In the present study, when the diameter of dysmorphic intratumoral vessels was greater than 3 mm, they were considered present. The cut-off value of 3 mm was arbitrarily determined to facilitate the differentiation between dysmorphic intratumoral vessels and normal hepatic arteries. Third, the estimated lung dose depends on the LSF as well as the target tissue volume and the desired absorbed dose. Thus, when the tumor is larger than 11 cm, TARE cannot be performed in most patients with 15-20% LSF.

In conclusion, dysmorphic intratumoral vessel is a novel imaging predictor for high LSF cases. Patients with elevated LSF values ​​can be predicted with high accuracy and specificity using pre-procedural cross-sectional imaging results.

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